Skin diseases such as contact hypersensitivity, atopic dermatitis, and psoriasis are characterized by hyperproliferative and inflammatory skin disorders. A large population suffers from these disorders, psoriasis; for example, afflicts approximately 2% of the population in Western countries [Ziboh, V.A. Psoriasis: Hyperproliferative/Inflammatory skin disorder, Drug Development Research 13: 137-146, (1988)]. Human skin diseases like psoriasis are characterized by histopathologically distinct patterns of infiltration by T cells, B cells, monocytes and granulocytes. These leukocyte cell infiltrations are the consequence of expression of intercellular adhesion molecules and release of cytokine and chemotactic factors by nonhematopoietically derived cells (e.g. keratinocytes) of the skin which in turn augment hyperplasia.
Current treatment of immunologically mediated skin disorders involves the use of antiinflammatory agents such as glucocorticoids and antiproliferative agents such as methotrexate, 5-fluorouracil, and retinoids. Recently, use of the immunosuppressive agent cyclosporin A has been reported to give clinical improvement of psoriasis [Ellis, J. Am. Med. Assoc. 256: 3110-3116, (1986)]. However, its usefulness in psoriasis is limited due to high incidence of nephrotoxicity [Ellis, New England J. Med. 324: 277-84, (1991)], and the observation of relapse after cessation of the treatment with cyclosporin A [Griffiths, J. Am. Acad. Dermatol. 23: 1242-1247, (1990)].
Rapamycin, a macrocyclic triene antibiotic produced by Streptomyces hygroscopicus [U.S. Pat. No. 3,929,992] has been shown to prevent the formation of humoral (IgE-like) antibodies in response to an albumin allergic challenge [Martel, R., Can. J. Physiol. Pharm. 55: 48 (1977)], inhibit murine T-cell activation [Staruch, M., FASEB 3: 3411 (1989)], and prolong survival time of organ grafts in histoincompatible rodents [Morris, R., Med. Sci. Res. 17: 877 (1989)].